De Novo Donor-Specific HLA Antibodies After Kidney Transplantation Are Associated With Donation After Circulatory Death and HLA-DQ Mismatch

G. Dreyer,¹ D. Roelen,² S. Brand-Schaaf,² O. Dekkers,³ M. Reinders,¹ F. Claas,² J. de Fijter.¹

¹Nephrologie, LUMC, Leiden, Netherlands
²Immunohaematology and Blood Transfusion, LUMC, Leiden, Netherlands
³Clinical Epidemiology, Aarhus Medical Center, Aarhus C, Denmark.

Meeting: 2015 American Transplant Congress

Abstract number: A111

Keywords: HLA antibodies, Immunosuppression, Kidney transplantation, Rejection

Session Information

Session Name: Poster Session A: Kidney Antibody Mediated Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

Introduction: De novo donor-specific HLA-antibodies (dnDSA) have been associated with rejection and inferior kidney graft survival. The purpose of this study was to investigate the incidence of dnDSAs in relation to different randomized treatments and the clinical relevance of dnDSA in relation to rejection and graft loss.

Methods: 429 kidney transplant recipients of living, brain (DBD) or circulatory death (DCD) donors with standard immunological risk (PRA <60%) were identified from 5 different randomized trials. All patients received IL2-RB induction and were stratified according to time of randomization: de novo: day 1 (N=182), early: month 6 (N=77) or late: >6 months (N=170) after transplantation between AUC-guided standard triple or interventional therapy (CNI/MMF withdrawal, conversion to mTor inhibitor). DSAs were measured before transplantation and 12 months after intervention using Luminex single antigen beads (One Lambda).

Results: Overall 12% developed dnDSA, 78% were HLA-class II, predominantly anti HLA-DQ. In the de novo group 43% developed dnDSAs, in the early group 22% and in the late group 35%. Multivariate analysis showed no significant influence of therapy or timing of therapy switch. Multivariate analysis indicated an association between DCD and dnDSA formation (OR 1.38, p=0.034). There also was a significant correlation between HLA-DQ mismatch and dnDSAs (OR 1.90, p=0.035). 64 Patients with both a DCD donor and DQ mismatch were at highest risk: 17.2% formed HLA class II antibodies compared to 5.7% in 53 patients with DBD and DQ mismatch. In addition a significant relation was found between dnDSAs and treated biopsy-proven rejection (tBPAR) (OR 2.27, p=0.012) and death-censored graft loss (OR 3.32, p=0.033). Kaplan Meier analysis demonstrated inferior 15 years graft survival with dnDSAs (p=0.05).

Conclusion: In this cohort intervention in immunosuppressive regimen did not effect the appearance of dnDSA. Main risk factors for dnDSAs were DCD and HLA-DQ mismatch. Ischemia/reperfusion injury might have caused induction of HLA-DQ expression on endothelial cells. The presence of dnDSAs was correlated with tBPAR and inferior graft survival. More data including MFI-thresholds and complement-binding capacity are currently under evaluation.

To cite this abstract in AMA style:

Dreyer G, Roelen D, Brand-Schaaf S, Dekkers O, Reinders M, Claas F, Fijter Jde. De Novo Donor-Specific HLA Antibodies After Kidney Transplantation Are Associated With Donation After Circulatory Death and HLA-DQ Mismatch [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/de-novo-donor-specific-hla-antibodies-after-kidney-transplantation-are-associated-with-donation-after-circulatory-death-and-hla-dq-mismatch/. Accessed November 21, 2024.

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